Phase separator for continuous flow operation

ABSTRACT

A separator for separating multiphase fluid streams. The separator includes inlet and outlet means having wettable means positioned within the inlet means to direct the fluid to the outlet means.

United States Patent [191 Isreeli et a].

AlR-SEGMENTED STREAM OF AQUEOUS AND ORGANIC PHASES PHASE SEPARATOR FOR CONTINUOUS FLOW OPERATION Inventors: Jack lsreeli, Mamaroneck; Aaron Kassel, Tarrytown; Anthony F.

Buccafuri, Pomona, all of NY.

Assigneez' Technicon Instrument Corporation,

Tarrytown, NY.

Filed: Oct. 13, 1971 Appl. No.: 188,830

US. Cl. 210/532, 23/253 Int. Cl. B0ld 12/00, G01n 29/02 Field of Search 23/230, 253; 210/65,

[451 July 3, 1973 [56] References Cited UNITED STATES PATENTS 2,214,248 9/1940 Hawley 210/532 2,903,342 9/1959 Buchler... 210/537 3,627,495 12/1971 Adler 23/253 Primary Examiner-Charles N. Hart AttorneyS. P. Tedesco et al.

[5 7] ABSTRACT A separator for separating multiphase fluid streams. The separator includes inlet and outlet means having wettable means positioned within the inlet means to direct the fluid to the outlet means.

8 Claims, 6 Drawing Figures AQUEOUS PHASE AND AIR PLUS SOME ORGANIC BY DIFFERENCE [AIR FOR SEGMENTAT/ON ORGAN/C PHASE sum-mm 3191a SHEEI 2 0F 3 ORGAN/C PHASE AND AIR PLUS A /R F0 R SOME AQUEOUS SEGMENTA T/ON BY DIFFERENCE F m w E mwflm ME A GR ET P s 7 m A SEGMENTED DE-BUBBLE BY PUMPING A/R FOR F SEGMENTA-T/ON STREAM OF PHASE AlR-SEGMENTED E DReA/v/c SEGMENTED STREAM OF AQUEOUS AND ORGAN/C PHASES AQUEOUS AND SOME ORGAN/C BY DIFFERENCE DE-BUBBLE A/R FOR rSEGMENTAT/ON BY PUMPING FIG. 5

Aczuzfous PHASE F O M w T S ORGAN/C AND SOME SEGMENTED STREAM OF AQUEOUS AND ORGAN/C HA RES AQUEOUS BY DIFFERENCE PHASE SEPARATOR FOR CONTINUOUS FLOW OPERATION BACKGROUND OF THE INVENTION 1. Field of the Invention This invention relates to a new and improved phase separator for continuous flow operation.

2. Description of the Prior Art Although phase separators for continuous flow-operation are known, it may be understood that the same will, in general, be found to have relatively large holdup volumes which function to limit the usefulness thereof in automated analysis apparatus. More specifically, and for use, for example, in automated analysis apparatus wherein a series of different samples which constitute an aqueous phase are formed into a stream and automatically and successively treated, as by solvent extraction, through interaction with a solvent phase, it may be understood that the relatively large hold-up volumes of the included prior art phase separators will function to unduly limit the sample analysis rate at which such analysis apparatus may be operated, and will not, in every instance, provide the complete phase separation as is required to insure the consistent accuracy of the sample analysis results. Too, said relatively large hold-up volumes are not particularly conductive to the required maintenance of sample integrity with resultant possility of unacceptable inter-sample contamination.

OBJECTS OF THE INVENTION It is, accordingly, an object of this invention to provide a new and improved phase separator for cintinuous flow operation'having a very small hole-up volume.

Another object .of this invention is the provision of a phase separator as above including means to promote complete phase separation.

Another object of the invention is the provision of a phase separator as above which, when utilized with a stream of a series of different samples, includes means to preserve sample integrity and inhibit inter-sample contamination.

A further object of this invention is the provision of a phase separator as above which is particularly adaptable for use in an automated, continuous flow sample anslysis system which functions to determine the morphine level in a succession of different urine samples at a particularly high analysis rate.

SUMMARY OF THE DISCLOSURE As disclosed herein, the new and improved phase separator for continuous flow operation of the invention takes the form of a fitting of a suitably inert material in the nature of glass having a body portion, an inlet for a multi-phase stream which includes aqueous and organic phases, and first and second outlets for said phases. Means which are preferentially wettable by said organic phase to promote phase separation and the accumulation of said organic phase and flow thereof to the outlet therefor are provided and take the form of a generally elongate member which is insertable into said separator to extend generally between said inlet and the outlet for said organic phase. For use in those instances wherein the organic is the heavier of the phases, the outlet therefore is disposed at a lower level than the aqueous phase outlet, while the reverse is true for instances wherein the aqueous phase is the heavier to thereby, in either event, take full advantage of the natural separational effects of gravity. Means may be included to segment one of the resultant separated phase streams with a suitable separating fluid when the separator is used in automated, sample analysis systems.

An application of the separator of'the invention in an automated analysis system directed toward the determination of the morphine levels in a stream of different urine samples on a continuous flow basis is disclosed to clearly illustrate the advantages provided by the separator.

DESCRIPTION OF THE DRAWINGS The above and other objects and significant advantages of the invention are believed made clear by the following detailed description thereof taken in conjunction with the accompanying drawings wherein:

FIG. 1 is a longitudinal cross-sectional view taken through a first embodiment of the phase separator of the invention;

FIG. 2 is a cross-sectional view taken along line 2-2 of FIG. 1;

FIG. 3 is a longitudinal cross-sectional view taken through a second embodiment of the phase separator of the invention;

FIG. 4 is a longitudinal cross-sectional view taken through a third embodiment of the phase separator of the invention;

FIG. 5 is a longitudinal cross-sectional view taken through a fourth embodiment of the phase separator of the invention; and

FIG. 6 is a schematic flow diagram illustrating a utilization of the phase separator of the invention in an automated sample analysis system.

DETAILED DESCRIPTION OF THE INVENTION Referring now to FIGS. 1 and 2, a first embodiment of a new and improved phase separator for organicaqueous phase separation in continuous flow analysis is indicated generally at 10 and comprises an inlet 12 and outlets I4 and 16. The separator 10 is preferably made of glass. An insert 18 of a material which is preferentially wet by said organic phase is disposed as shown within the separator by friction fit, and the insert includes a nib or the like 20 to maintain the same positioned substantially as depicted. For use with a polar aqueous phase and a non-polar organic phase, the insert 18 is made of a suitable material in the nature of Teflon or polyethylene having a non-polar surface.

A stream 22 of alternating, substantially immiscible organic and aqueous (O and A) liquid phase segments, in which said organic phase is the heavier, is flowed as by pumping into separator inlet 12 through conduit 24. For a typical continuous flow utilization 'of the separator 10, the stream 22 will preferably be segmented as shown by a suitable separating fluid in the nature of air, and will consist of successive treated samples of an aqueous phase, a solute from which has been extracted into an organic solvent phase by preferential partitioning during flow through a mixing coil or the like as well understood by those skilled in the continuous flow solvent extraction art.

As the stream 22 enters the separator 10, the nonpolar surface of the insert 18 will be preferentially wet by the non-polar solvent phase, to the substantial exclusion of the polar aqueous phase, thereby causing the solvent phase to coalesce and pool at and on said insert.

This preferential wetting, in conjunction with the natural separational effects of gravity on said solvent phase, will cause the same to follow the insert to the lower portion of the separator for flow therefrom through outlet 16.

A very small portion of the organic phase, plus substantially all of the aqueous phase and the air will flow by difference from the separator through outlet 14. Segmentation of the resultant organic phase stream for wash purposes and for maintaining sample integrity in a continuous flow separation system may be readily effected by the introduction of a suitable separating fluid in the nature of air to said stream as indicated through capillary 26, although it is believed clear that such segmentation is not essential to efficient phase separation. In the same manner, it is believed clear that the incoming stream 22 need not be air-segmented for efficient operation of the separator 10.

A second embodiment of the separator is indicated at 30 in FIG. 3 and comprises an inlet 32, outlets 34 and 36, and the insert 18. The separator 30 is for use when the aqueous phase is the heavier, and would be particularly applicable for hase separation following the back-extraction of a solute from the organic to aqueous phases on a continuous flow basis. As the stream 22 enters the separator 30, the solvent phase again preferentially wets and follows the insert 18, to the substantial exclusion of the aqueous phase for flow by difference, with the air and a very small portion of the aqueous phase, from the separator 30 through outlet 34. The substantial majority of the aqueous phase will, meanwhile, collect as shown under the influence of gravity in the lower portions of the separator 30 for flow therefrom through outlet 36. Air-segmentation of the resultant aqueous phase may again be effected through a capillary as here indicated at 38.

A third embodiment of the separator is indicated at 40 in FIG. 4 and comprises an inlet 42 and outlets 44 and 46. The insert, here indicated at 48, comprises nibs 50 and 52 for positioning. A debubbler is indicated at 54 and in included only when the incoming stream 56 is air-segmented. The separator 40 is for use when the organic phase is the lighter in, for example, acontinuous flow solvent extraction process as described with regard to FIG. I. As the stream 56 enters the separator 40, the organic phase will preferentially wet and follow the insert 48 with the result that the major portion thereof, as air segmented if required through capillary 58, will flow from the separator through outlet 44. The aqueous phase with a very small portion of the organic phase will flow by difference from the separator through outlet 46.

A fourth embodiment of the separator is indicated at 60 in FIG. 5 and comprises an inlet 62 and outlets 64 and 66. The insert, here indicated at 68, comprises nibs 70 and 72 for positioning within the separator as shown. A debubbler is indicated at 74 and is included only when the incoming stream 76 is air-segmented.

let conduit 66. The ligher aqueous phase will meanwhile remain substantially above the preferentially wetted insert 68 for flow from the separator, as airsegmented if desired through capillary 76, through outlet 64.

Purging" of each of the disclosed separator embodiments prior to the utilization thereof may, of course, be readily effected by the initial flow therethrough, for a sufficient period of time, of the phase which preferentially wets the insert to insure the absence of any of the other phase in the separator prior to the commencement of operation.

Of particular advantage with regard to each of the disclosed separator embodiments is the fact the holdup volume, or volume thereof which must be filled for each phase separation, is substantially minimal, whereby the operational rates of the separators in terms of the number of treated samples which may be processed thereby per unit time is maximized. Too, the substantially complete separation provided with regard to the separated phase of interest is, of course, of particularly significant advantage as should be obvious.

A utilization of the separation of the invention in a system for the automated fluorometric determination of the morphine levels in urine samples to determine drug use on the part of the urine donorsis illustrated schematically in FIG. 6 and, briefly described, comprises the supply of a continuous air-segmented stream of successive urine sample segments buffered to appropriate pH (the aqueous phase), generally alternating segments of a heavier solvent mixture (the organic phase), and appropriately spaced segments of a suitable wash liquid, respectively, to and through a suitable mixing coil 78 to effect the extraction of the free morphine base solute from the buffered urine sample segments to the adjoining solvent mixture segments.

through preferential solute partitioning. Following this, the stream is flowed through the separator 10 of MG. 1 for separation of the organic phase as described, and which now contains the morphine solute of interest, and immediate re-segmentation of this phase with air through capillary 26 to thereby maintain sample integrity and inhibit inter-sample contamination.

Thereafter, a buffer solution at the same appropriate pH is added to the organic phase and the resultant stream flowed through mixing coil 82 to effect a cleansing of the organic phase by wash-extraction or back-extraction of amino acids and like compounds indigin'ous to urine therefrom into the buffer solution aqueous phase. Separation of the organic phase from this buffer is theneffected in separator 10. and is followed as indicated by the re-segmentation with air of the solvent phase.

A strongly alkaline solution is then added as indicated to the solvent phase stream and the resultant stream flowed through a mixing coil 86 to effect backextraction of the morphine solute into this newly added alkaline solution aqueous phase. Following this, the resultant stream is flowed through the separator 60 of FIG. 5, wherein the same is de-bubbled by debubbler 74 and the organic phase and a very small portion of the aqueous phase flowed to waste by difference through outlet 66, while the major portion of said aqueous phase, now containing the morphine solute of interest, is immediately re-segmented with air and flowed from separator 60 'to and through pump 88.

A buffer at the appropriate pH is then added to the aqueous phase and the same divided as indicated into two streams. A pseudo-morphine solution to dimerize the morphine is added to one of said streams, and distilled water added to the other to provide a blank channel, whereupon said streams are simultaneously applied to and analyzed in fluorometers 90 and 92. The results of these analayses are applied as indicated to a strip chart recorder to provide a readily readable and reproducible record of the morphine level in each of said urine samples.

A general discussion of the methodology involved in the determination of morphine levels in urine samples is provided in the article Automated Analysis for Drugs in Urine by D. V. Blackmore, et al., as pub lished in CLINICAL CHEMISTRY, Volume 17, No. 9, of 1971; and such article is hereby incorporated by reference herein.

Utilization as described of the separator of the invention in an automated analysis system may be understood to make possible the operation of said system at a rate of between 40 and 60 samples per hour with the same clarity of analysis results as could be provided by such system utilizing the separators of the prior art at a maximum rate of between only and samples per hour.

Although disclosed as comprising a separately formed preferentially wettable insert, it is believed clear that the separator of the invention could, alternatively, be fabricated with said insert formed as an integral part thereof.

T00, and although disclosed by way of illustrative example as applied to the determination of morphine levels in urine samples, it is believed clear that the phase separator of the invention is by no means limited thereto, but rather, is advantageously utilizable for the phase separation function in a very wide variety of other and different applications.

While we have shown and described the preferred embodiment of our invention, it will be understood that the invention may be embodied otherwise than as herein specifically illustrated or described, and that certain changes in the form and arrangement of parts and in the specific manner of practicing the invention may be made without departing from the underlying idea or principles of this invention within the scope of the appended claims.

What is claimed is:

l. A separator for separating phases from a multiphase fluid stream on a continuous flow basis comprising, an inlet for said multi-phase stream, first and second outlets, and means in said separator which are preferentially wettable by one of said phases to promote phase separation and the accumulation of said one phase on and around said means and the flow of said phase to a predetermined one of said outlets, said last-mentioned means extending generally from said inlet and to said predetermined one of said outlets, so as to direct said one phase to said predetermined one of said outlets.

2. A separator as in claim 1 wherein, said multi-phase stream comprises an aqueous phase and an organic phase, and wherein said means are preferentially wettable by said organic phase.

3. A separator as in claim 1 wherein, said multi-phase stream comprises a polar phase and a non-polar phase, and wherein said means comprise a non-polar surface so as to be preferentially wettable by said non-polar phase.

4. A separator as in claim 1 wherein, said lastmentioned means comprises a generally elongate member which is insertable into said separator to extend generally from said inlet and to said predetermined one of said outlets.

5. A separator as in claim 2 wherein, said organic phase is heavier than said aqueous phase, said predetermined one of said outlets is disposed at a lower level than the other of said outlets.

6. A separator as in claim 2 wherein, said aqueous phase is heavier than said organic phase, said predetermined one of said outlets is disposed at a higher level than the other of said outlets.

7. A separator as in claim 1 further comprising, means to introduce a separating fluid after phase separation to segment the phase which flows to said predetermined outlet. I

8. A separator as in claim 1 further comprising, means to introduce a separating fluid after phase separation to segment the phase which flows to the other of said outlets. 

1. A separator for separating phases from a multiphase fluid stream on a continuous flow basis comprising, an inlet for said multi-phase stream, first and second outlets, and means in said separator which are preferentially wettable by one of said phases to promote phase separation and the accumulation of said one phase on and around said means and the flow of said phase to a predetermined one of said outlets, said last-mentioned means extending generally from said inlet and to said predetermined one of said outlets, so as to direct said one phase to said predetermined one of said outlets.
 2. A separator as in claim 1 wherein, said multi-phase stream comprises an aqueous phase and an organic phase, and wherein said means are preferentially wettable by said organic phase.
 3. A separator as in claim 1 wherein, said multi-phase stream comprises a polar phase and a non-polar phase, and wherein said means comprise a non-polar surface so as to be preferentially wettable by said non-polar phase.
 4. A separator as in claim 1 wherein, said last-mentioned means comprises a generally elongate member which is insertable into said separator to extend generally from said inlet and to said predetermined one of said outlets.
 5. A separator as in claim 2 wherein, said organic phase is heavier than said aqueous phase, said predetermined one of said outlets is disposed at a lower level than the other of said outlets.
 6. A separator as in claim 2 wherein, said aqueous phase is heavier than said organic phase, said predetermined one of said outlets is disposed at a higher level than the other of said outlets.
 7. A separator as in claim 1 further comprising, means to introduce a separating fluid after phase separation to segment the phase which flows to said predetermined outlet.
 8. A separator as in claim 1 further comprising, means to introduce a separating fluid after phase separation to segment the phase which flows to the other of said outlets. 